Heretofore, production of foreign proteins by using gene recombination technology has been actively carried out by using microorganisms including Escherichia coli, budding yeast (Saccharomyces cerevisiae), a microorganism of the genus Bacillus, etc., animal cells, plant cells, or insect cells. Proteins derived from various organisms are considered as objects of the production, and many proteins have already been produced industrially by using such organisms and have been used for pharmaceuticals, etc. Particularly, the secretory production of a foreign protein is preferred from the view point of easiness in purification as compared with a case wherein produced foreign proteins are accumulated in inside of a cell, and is advantageous since proteins produced by secretion enter into a secretory pathway of a host cell and are subjected to an appropriate treatment such as disulfide bond formation or saccharide chain formation thereby to form a conformational structure quite similar or identical to that of natural proteins.
By producing a foreign protein in a state where a secretion signal peptide is added to its N-terminal, the foreign protein can be produced by secretion. For example, as a secretion signal recognized by fission yeast Schizosaccharomyces pombe (hereinafter referred to as S. pombe), a polypeptide derived from a secretion signal of a mating pheromone (P-factor) precursor involved in the mating of S. pombe may be mentioned (refer to Patent Document 1). When cultivating a S. pombe transformant introduced with a structural gene encoding a fusion protein having the polypeptide at the N-terminal of a foreign protein, the produced fusion protein is separated into a signal peptide and the foreign protein in the Golgi apparatus or the endoplasmic reticulum (ER), and accordingly, the foreign protein will be secreted from the host cell into a culture broth.
Further, with regard to the increase in the production amount of secretory proteins, it has been known that co-expression of a foreign secretory protein with PDI1 increases the secretory production amount (the amount of a secreted protein, among the proteins produced by the host) of the secretory protein (refer to Non-Patent Document 1). PDI1 (Protein disulfide isomerase 1) has a molecular chaperone function, and is a protein localized to the ER.